A recent trend in studies on pharmaceutical protein production is the increasing use of transgenic animals. Some attempts were made to accumulate suitable foreign proteins in goats' or sheep's milk. These techniques are already in practical use. The disadvantages of using mammals, such as goats and sheep, are: a large rearing space; a long period to sexual maturity; and a long time-scale for setting up a production line. Alternatively, birds, such as chickens, have been used in an attempt to accumulate a suitable foreign protein in their egg white. Chickens are useful because a large rearing space is not required; hens begin to lay eggs at only about 6 months of age; and their safety is confirmed from our long history of diets. In order to accumulate a suitable foreign protein in egg white, a site-specific promoter for an egg white-localized protein, such as an ovalbumin promoter (Patent Literature 1) or an ovomucoid promoter (Patent Literature 2), is usually used. Or, an actin promoter that allows a protein to be systemically expressed can also be used (Patent Literature 3).
Promoters for proteins that are accumulated in egg white naturally induce oviduct-specific gene expression. Accordingly, they are very useful promoters for accumulation of suitable foreign proteins in egg white. Unfortunately, when they are used in a recombinant DNA technique to express suitable foreign proteins in egg white, their oviduct-specific expression does not allow us to quantify the expression of the suitable foreign proteins until hens lay eggs. It is noted that these promoters do not allow quantification of the expression of suitable foreign proteins, for example, in blood samples from sites other than the oviduct (Non Patent Literature 1, FIG. 3). This means that the productivity of hens as biofactories cannot be checked until hens reach sexual maturity, and that all transgenic hens should be reared until they reach sexual maturity. Effort and costs for rearing low-productive hens until their sexual maturity are serious problems.
By contrast, in the case of using an actin promoter, which allows a target protein to be expressed in the cells throughout the chicken's body, it is possible to predict the amount of protein to be produced to some extent by measuring the concentration of the protein in blood. This enables selection of individuals with high expression before they reach sexual maturity. Unfortunately, some suitable foreign proteins or their physiological functions can be a great burden on chickens when the proteins are systemically expressed. Great burdens on chickens are known and include a decreasing hatching rate, a decreasing survival of hatched individuals, a decreasing reproductive capacity, and a decreasing egg laying ability. Such effects on the chicken's health are expected to greatly affect the production costs.